PTH receptor signaling in osteoblasts regulates endochondral vascularization in maintenance of postnatal growth plate

J Bone Miner Res. 2015 Feb;30(2):309-17. doi: 10.1002/jbmr.2327.

Abstract

Longitudinal growth of postnatal bone requires precise control of growth plate cartilage chondrocytes and subsequent osteogenesis and bone formation. Little is known about the role of angiogenesis and bone remodeling in maintenance of cartilaginous growth plate. Parathyroid hormone (PTH) stimulates bone remodeling by activating PTH receptor (PTH1R). Mice with conditional deletion of PTH1R in osteoblasts showed disrupted trabecular bone formation. The mice also exhibited postnatal growth retardation with profound defects in growth plate cartilage, ascribable predominantly to a decrease in number of hypertrophic chondrocytes, resulting in premature fusion of the growth plate and shortened long bones. Further characterization of hypertrophic zone and primary spongiosa revealed that endochondral angiogenesis and vascular invasion of the cartilage were impaired, which was associated with aberrant chondrocyte maturation and cartilage development. These studies reveal that PTH1R signaling in osteoblasts regulates cartilaginous growth plate for postnatal growth of bone.

Keywords: GROWTH PLATE; PARATHYROID HORMONE; POSTNATAL BONE GROWTH; VASCULARIZATION.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Count
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Gene Expression Regulation, Developmental
  • Growth Plate / blood supply*
  • Growth Plate / growth & development*
  • Growth Plate / metabolism*
  • Hypertrophy
  • Mice, Knockout
  • Neovascularization, Physiologic*
  • Osteoblasts / metabolism*
  • Osteogenesis
  • Receptor, Parathyroid Hormone, Type 1 / deficiency
  • Receptor, Parathyroid Hormone, Type 1 / metabolism*
  • Signal Transduction*

Substances

  • Receptor, Parathyroid Hormone, Type 1